Fibroblast growth factors (FGFs) belong to a polypeptide family coded by the FGF gene family, and having different biological activity and having relevant structures. So far the FGF family has been found to have 22 members. Fibroblast growth factor receptors (FGFRs) are a class of trans-membrane tyrosine kinase receptors, which mediate FGF signal transmission to the cytoplasm. Currently 4 FGFRs of independent gene codes have been confirmed, i.e., FGFR1, FGFR2, FGFR3, and FGFR4. They are all single chain glucoprotein molecules comprised of an extracellular region, a trans-membrane region and an intracellular region. The receptor-ligand interaction causes receptor dimerization and autophosphorylation, and the formation of a complex with a membrane binding protein and a cytoplasmic helper protein, thereby mediating conduction of multiple signals. The FGFR-FGF signal conducting system plays an important role in a great many biological processes such as cell proliferation, differentiation, migration, angiogenesis and tissue repair.
FGFR4 is a main FGF receptor subtype in the liver. 10 out of more than 20 fibroblast growth factors (FGFs) that have been discovered up to now can bind to FGFR4, where only FGF19 binds to FGFR4 specifically. Studies in recent years show that changes, such as overexpression, mutation, translocation and truncation, of FGFR4 are associated with the progress in various human cancer, including rhabdomyosarcoma, renal cell carcinoma, myeloma, breast cancer, gastric cancer, colon cancer, bladder cancer, pancreas cancer and hepatocellular cancer.
Therefore, it can be predicted that the selective inhibition of FGFR4 can be used to treat the above cancer, and particularly tumors where an activated mutant of the receptor tyrosine kinase is present or the receptor tyrosine kinase is upregulated are especially sensitive to this type of inhibitors.